The central nervous system effects of many neruropharmaceuticals and in particular the action of addictive drugs is only partially understood. We propose to develop a system that uses the acute behavioral responses of Drosophila to study addictive drugs, specifically "crack" cocaine. Acute behavioral responses to cocaine in flies have similarities to those in vertebrates. We have a behavioral assay for rapid assessment of acute sensitivity to vaporized free base cocaine. Drosophila has a highly developed genetic system which provides many tools that make facile a forward genetic screen for altered sensitivity to drug responses. The aims of this proposal are: 1) to isolate mutants that respond abnormally to the acute stimulant properties of cocaine; 2) to develop secondary assays that refine our selection of mutants to those most pertinent to the stimulant- induced effects of cocaine; 3) to clone and characterize genes that modulate these behavioral responses in flies. Our genetic analysis should yield tools for the study of the molecular and biochemical mechanisms that underlie stimulant induced responses.